Randomized phase III study of weekly <i>nab</i>-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT).

LBA148 Background: nab-Paclitaxel (nab-P, 130 nm albumin-bound paclitaxel) provides tumor selective localization via transcytosis across the endothelium, potential tumor uptake via macropinocytosis, and improved pharmacokinetics vs cremophor-paclitaxel. In vitro, nab-P increased tumoral gemcitabine (G) levels, and in a phase I/II study in metastatic pancreatic cancer (mPC) nab-P + G showed promising activity. Methods: Patients (pts) with mPC were randomized to nab-P 125 mg/m 2 , followed by G 1000 mg/m 2 on days 1, 8, and 15 every 4 weeks or G 1000 mg/m 2 weekly for 7 weeks (cycle 1), then on days 1, 8, and 15 every 4 weeks (≥ cycle 2). For the primary endpoint of overall survival (OS), 608 events from 842 patients provided a power of 0.9 to detect a HR of 0.769 (2-side α = 0.049). Results: 861 pts received therapy. Baseline pt characteristics were well balanced. Median age was 63 years, Karnofsky performance status was 90-100 in 60% and ≤80 in 40% of pts, 43% had head of pancreas lesions, 84% had liver and 39% had lung metastases, and 52% of pts had CA19-9 ≥59 x ULN. Treatment duration was 4 vs 3 months in nab-P + G vs G. The relative protocol G dose was 75% vs 85% in nab-P + G vs G; nab-P dose was 81%. OS, progression-free survival (PFS), time to treatment failure (TTF), and overall response rate (ORR) were significantly improved in the nab-P + G arm (Table). Most common grade ≥3 AEs were neutropenia (38% vs 27%), fatigue (17% vs 7%), and neuropathy (17% vs 1%) in the nab-P + G vs G arms. Grade ≥3 neuropathy improved to grade ≤1 in 29 days. Febrile neutropenia was reported in 3% (nab-P + G) vs 1% (G) pts. Conclusions: In this multinational, multiinstitutional study, nab-P + G was well tolerated and superior to G with statistically significant and clinically meaningful results in all endpoints and across subgroups. Clinical trial information: NCT00844649. [Table: see text]